IRAP识别了MHC I类交叉呈现所需的内体
Loredana Saveanu1, Oliver Carroll, Mirjana Weimershaus
1INSERM, U580, 75015 Paris, France; Université Paris Descartes, Faculté de Médecine René Descartes, 75015 Paris, France.
概括
胰岛素调节的氨基酶 (IRAP) 在交叉呈现中发挥着关键作用,通过切割内体中的来获得主要基因相容性复合体 (MHC) I 类分子. 这一发现澄清了参与抗原呈现的细胞区.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 蛋白质稳定性 蛋白质稳定性
背景情况:
- 主体组织相容性复合体 (MHC) I 类分子呈现的从细胞质蛋白到细胞毒性T 淋巴细胞.
- 交叉呈现允许树突细胞通过MHC类I呈现外源抗原,但涉及的细胞区域尚未完全理解.
研究的目的:
- 研究剪切在细胞交叉呈现机制中的作用.
- 为了确定在交叉呈现途径中涉及的特定细胞区和酶.
主要方法:
- 免疫光显微镜用于在人类树突细胞中定位IRAP和MHC I类.
- 基因编辑CRISPR/Cas9以创建缺少IRAP的树突细胞.
- 在体外和体内测试以评估交叉呈现效率.
主要成果:
- 胰岛素调节的氨基酶 (IRAP) 局部化到Rab14+内体区,与MHC I类分子相互作用.
- 在体外和体外模型中,IRAP缺乏导致交叉呈现受损.
- 通过MHC I类的内源性呈现不受IRAP缺乏的影响.
结论:
- IRAP对于高效的交叉呈现至关重要,它在内体区中起作用,用于最终的剪切.
- 提出了两种不同的蛋白酶体依赖交叉呈现的途径:一种涉及内分体中的IRAP,另一种使用内分体网膜居民氨基酶.
相关概念视频
Intralumenal Vesicles and Multivesicular Bodies
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
Antigen Processing Pathways
MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
MHC Class I: Presenting Endogenous...
Recycling Endosomes and Transcytosis
The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
Antigens Involved in Adaptive Immunity
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
The Early Endosome: Endocytosis of Transferrin
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
Rab Cascades
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.


